Abstract

RBM10 is an RNA-binding protein that regulates alternative splicing (AS). This protein localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs). We investigated the biological significance of RBM10 localization to S1-1 NBs, which is poorly understood. Our analyses revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs acted synergistically and were sufficient for localization of RBM10 to S1-1 NBs. Furthermore, the C2H2 ZnF not only acted as an NBTS, but was also essential for regulation of AS by RBM10. RBM10 did not participate in S1-1 NB formation. We confirmed the previous finding that localization of RBM10 to S1-1 NBs increases as cellular transcriptional activity decreases and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in these structures via its NBTSs when cellular transcription decreases. We propose that the NB-targeting activity of the C2H2 ZnF is induced when it is not bound to pre-mRNA or the splicing machinery complex under conditions of reduced transcription.

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